chr1-41096613-T-G

Variant names:

• chr1-41096613-T-G
• rs2024859
• NM_001394311.1:c.745+16670A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394311.1(SCMH1):​c.745+16670A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,096 control chromosomes in the GnomAD database, including 55,340 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (55340 hom., cov: 30)
• Consequence: SCMH1 NM_001394311.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 8 publications found

Genes affected

SCMH1 (HGNC:19003): (Scm polycomb group protein homolog 1) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to act upstream of or within anterior/posterior pattern specification; chromatin remodeling; and spermatogenesis. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCMH1	NM_001394311.1	c.745+16670A>C		intron_variant	Intron 8 of 15	ENST00000695335.1	NP_001381240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCMH1	ENST00000695335.1	c.745+16670A>C		intron_variant	Intron 8 of 15		NM_001394311.1	ENSP00000511813.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129072 AN: 151976 Hom.: 55292 Cov.: 30

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.857

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.851

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.849 AC: 129179 AN: 152096 Hom.: 55340 Cov.: 30 AF XY: 0.848 AC XY: 63055 AN XY: 74340

African (AFR) AF: 0.956 AC: 39697 AN: 41508

American (AMR) AF: 0.852 AC: 13008 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2710 AN: 3470

East Asian (EAS) AF: 0.965 AC: 4992 AN: 5174

South Asian (SAS) AF: 0.905 AC: 4356 AN: 4812

European-Finnish (FIN) AF: 0.784 AC: 8295 AN: 10576

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53416 AN: 67970

Other (OTH) AF: 0.849 AC: 1794 AN: 2112

Alfa AF: 0.768 Hom.: 2654

Bravo AF: 0.856

Asia WGS AF: 0.910 AC: 3165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.96
DANN	Benign	0.60
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2024859; hg19: chr1-41562285;